STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA
|ClinicalTrials.gov Identifier: NCT03829371|
Recruitment Status : Recruiting
First Posted : February 4, 2019
Last Update Posted : February 11, 2019
Multiple myeloma (MM) is a neoplastic disease deriving from an abnormal proliferation of monoclonal plasma cells in the bone marrow. The survival of MM patients varies from less than 6 months to more than 10 years depending on the stage of disease at diagnosis and prognostic factors. Three current standard treatments are approved for elderly or younger patients with significant comorbidities not eligible for autologous stem cell transplantation (ASCT): bortezomib-melphalan-prednisone (VMP), melphalan-prednisone- thalidomide (MPT) and lenalidomide with low-dose dexamethasone (Rd).
The consistent fraction of elderly patients with cancer and co-morbidities are at increased risk of developing frailty (the emergent geriatric syndrome), as well as physical and cognitive decline, with negative effect on nutrition and lifestyle, and eventually on responsiveness to and efficacy of treatments.
A frailty scale was recently described that categorized patients with MM as fit, intermediate or frail based on age, comorbidities, and physical and cognitive functioning. The frailty score was a predictor of death, progression of the disease, toxicity and drug discontinuation.
In this project, the investigators will compare available first line standard treatments, the triplet VMP versus the doublet Rd, in an unselected population of patients ≥ 65 years affected by MM in every day clinical practice. In the last decade, many novel and expensive drugs have been approved for this disease, yet the general older population is not adequately represented in validating trials. Nevertheless, the results and treatments derived from those trials have often been applied to the older population, with a high risk to produce a negative impact on patient functional capacity and ability to carry out daily tasks, cognitive function, depression status, nutritional condition, social situation/capability to stay at home and finally affecting their quality of life (QoL) and OS. The main aim of the project is to evaluate the best initial treatment for elderly MM patients and to compare benefits, risks, QoL and costs of currently available, standard treatments according to the frailty profile.
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: Velcade Drug: Melphalan Drug: Prednisone Drug: Lenalidomide Drug: Dexamethasone||Phase 4|
All patients will be randomized in a 1:1 ratio to receive:
- 1.3 mg/m2 subcutaneously on days 1, 4, 8, 11, 22, 25, 29 and 32 in cycles 1-4;
- 1.3 mg/m2 subcutaneously on days 1, 8, 22 and 29 in cycles 5-9.
- 9 mg/m2 orally on days 1, 2, 3 and 4 of each cycle.
- 60 mg/m2 orally on days 1, 2, 3 and 4 of each cycle. Each cycle is to be repeated every 42 days. Duration: Maximum 9 therapy cycles can be performed. After 9 cycles, patients will be observed until progression disease or the start of a new line of therapy.
- 25 mg orally on days 1-21 of each cycle.
- 40 mg orally on days 1, 8, 15 and 22 of each cycle. Each cycle is a 28-day cycles. Duration: patients will receive treatment until any sign of progression or intolerance.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||350 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A RANDOMIZED, MULTICENTER, OPEN LABEL STUDY COMPARING TWO STANDARD TREATMENTS, BORTEZOMIB-MELPHALAN-PREDNISONE (VMP) VS LENALIDOMIDE-DEXAMETHASONE (Rd) IN AUTOLOGOUS STEM CELL TRANSPLANTATION (ASCT) INELIGIBLE COMMUNITY POPULATION AFFECTED BY MULTIPLE MYELOMA (MM)|
|Actual Study Start Date :||January 3, 2019|
|Estimated Primary Completion Date :||January 3, 2023|
|Estimated Study Completion Date :||January 3, 2023|
Experimental: ARM A
- 9 mg/m2 orally on days 1, 2 3 and 4 of each cycle.
- 60 mg/m2 orally on days 1, 2, 3 and 4 of each cycle. Each cycle is a 42-day cycle. Duration: Maximum 9 cycles can be performed.
Experimental: ARM B
-25 mg orally on days 1-21 of each cycle.
-40 mg orally on days 1, 8, 15 and 22 of each cycle. Each cycle is a 28-day cycle. Duration: until PD or intolerance.
- Progression-free survival (PFS) [ Time Frame: 5 years ]Number of months from the date of randomization to the date of first observation of PD, or death from any cause as an event.
- Overall response rate (ORR) [ Time Frame: 5 years ]Overall response rate will include complete response (CR), very good partial response (VGPR) and partial response (PR) using the International Response Criteria. Responders are defined as subjects with at least a PR.
- Duration of response (DOR) [ Time Frame: 5 years ]Time between first documentation of response and PD. Responders without disease progression will be censored either at the time of lost to FU, at the time of death due to other cause than PD, or at the end of the study.
- Overall survival (OS) [ Time Frame: 5 years ]Time between randomization and death. Subjects who die will be censored at time of death as an event, regardless cause of death.
- Progression-free survival 2 (PFS2) [ Time Frame: 5 years ]Time from randomization to objective tumor progression on next-line treatment or death from any cause.
- Time to next therapy (TNT) [ Time Frame: 5 years ]Time to next therapy will be measured from the date of randomization to the date of next anti-myeloma therapy. Death due to any cause before starting therapy will be considered an event.
- Time to progression (TTP) [ Time Frame: 5 years ]Time to progression will be measured from the date of randomization to the date of first observation of PD, or deaths related to PD.
- Adverse events [ Time Frame: 5 years ]Safety will be evaluated by assessing the incidence, severity and type of AEs according to NCI-CTCAE v. 4.0.
- Rate of treatment discontinuation or death for toxicity [ Time Frame: 5 years ]Incidence of treatment discontinuation for toxicities as well as the rate of death for toxicity will be evaluated during the entire duration of the trial (toxicities evaluated according to NCI-CTCAE v. 4.0)
- Frailty score [ Time Frame: 5 years ]Validation of Myeloma Frailty Score (fit score=0; intermediate-fitness score=1, and frail score≥2) that assess comorbidities, cognitive and physical status in real population according to geriatric assessment and considering patients' non-Myeloma polydrug therapies.
- Quality of Life through Health-Related QoL (HRQoL) [ Time Frame: 5 years ]Quality of Life will be evaluated through questionnaire: EORTC-QLQ-C30 (a generic, multidimensional, cancer-specific QoL questionnaire).
- Quality of Life through Health-Related QoL (HRQoL) [ Time Frame: 5 years ]Quality of Life will be evaluated through questionnaire for MM patients: QLQ-MY20 (a specific 20- item MM module).
- Quality of Life through Health-Related QoL (HRQoL) [ Time Frame: 5 years ]Quality of Life will be evaluated through questionnaire: EQ-5D-5L (a generic assessment of five health categories and overall health score).
- Direct health related costs and indirect costs [ Time Frame: 5 years ]Health-related costs will be reported through Questionnaires For Patients Costs Evaluation reported in the protocol evaluating working activities.
- Direct health related costs and indirect costs [ Time Frame: 5 years ]Health-related costs will be reported through Questionnaires For Patients Costs Evaluation reported in the protocol evaluating care assistance.
- Direct health related costs and indirect costs [ Time Frame: 5 years ]Health-related costs will be reported through Questionnaires For Patients Costs Evaluation reported in the protocol evaluating health care visit.
- Risk of infectious complications [ Time Frame: 5 years ]Infectious risk complications will be evaluated through a scale evaluating the number of adverse events, severity, type of infection, need for hospitalization (yes/no), number of days of suspension of study treatment. All these data will be combined in the statistical analysis to combine different outcome of treatments.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03829371
|Contact: Mario Boccadoro, Prof.||firstname.lastname@example.org|
|Dipartimento di Biotecnologie Molecolari e Scienze per la Salute||Recruiting|
|Torino, TO, Italy, 10126|
|Contact: Mario Boccadoro, Prof. 00390116336107 email@example.com|